Survival, surveillance, and genetics in patients with Peutz-Jeghers syndrome: A nationwide study
Anne Marie Jelsig1, Thomas van Overeem Hansen1,2, Lene Bjerring Gede1
1Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Insights
Peutz-Jeghers syndrome (PJS) is a genetic disorder increasing cancer risk. This study found a high detection rate for pathogenic variants and significant cancer risks, highlighting the need for improved clinical care for PJS patients.
Area of Science:
- Genetics
- Oncology
- Hereditary Syndromes
Background:
- Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder.
- It is linked to increased cancer risk and mortality.
- Pathogenic variants (PVs) in the STK11 gene are known causes, but some patients lack identified PVs.
Purpose of the Study:
- To determine the genetic cause of PJS in Danish patients.
- To assess cancer risk, surveillance effectiveness, and survival rates in PJS.
- To identify gaps in current clinical management.
Main Methods:
- Genetic analysis of all known PJS patients in Denmark.
- Calculation of cumulative cancer and death probabilities.
- Analysis of cancer detection timing relative to surveillance schedules.
Main Results:
- A 96% detection rate for PVs was achieved in 56 identified PJS patients.
- Cancer probability reached 71% by age 70, with death probability at 69%.
- 92% of cancers were detected outside scheduled surveillance, indicating surveillance limitations.
Conclusions:
- PJS should be viewed as a general cancer predisposition syndrome.
- Current surveillance strategies for PJS require enhancement.
- Improved clinical care is essential for managing PJS complications and cancer risk.
Abstract:
Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%-15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2-83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.
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